Cohesion Group Approach for Evolutionary Analysis of TyrA, a Protein Family with Wide-Ranging Substrate Specificities

Abstract

SUMMARY Many enzymes and other proteins are difficult subjects for bioinformatic analysis because they exhibit variant catalytic, structural, regulatory, and fusion mode features within a protein family whose sequences are not highly conserved. However, such features reflect dynamic and interesting scenarios of evolutionary importance. The value of experimental data obtained from individual organisms is instantly magnified to the extent that given features of the experimental organism can be projected upon related organisms. But how can one decide how far along the similarity scale it is reasonable to go before such inferences become doubtful? How can a credible picture of evolutionary events be deduced within the vertical trace of inheritance in combination with intervening events of lateral gene transfer (LGT)? We present a comprehensive analysis of a dehydrogenase protein family (TyrA) as a prototype example of how these goals can be accomplished through the use of cohesion group analysis. With this approach, the full collection of homologs is sorted into groups by a method that eliminates bias caused by an uneven representation of sequences from organisms whose phylogenetic spacing is not optimal. Each sufficiently populated cohesion group is phylogenetically coherent and defined by an overall congruence with a distinct section of the 16S rRNA gene tree. Exceptions that occasionally are found implicate a clearly defined LGT scenario whereby the recipient lineage is apparent and the donor lineage of the gene transferred is localized to those organisms that define the cohesion group. Systematic procedures to manage and organize otherwise overwhelming amounts of data are demonstrated.

Cohesion Group Approach for Evolutionary Analysis of Aspartokinase, an Enzyme That Feeds a Branched Network of Many Biochemical Pathways

“…In addition, the true Alteromonadales in the lower Gammaproteobacteria (but not Marinobacter and Saccharophagus) all possess the three character states depicted, which are present throughout all of the lower Gammaproteobacteria (except for some cases of recent wholesale reductive evolution in pathogens and endosymbionts). These character states are two fusions (aroH I -tyrA [6] and trpD-trpC [90]), as well as a fully merged trp operon from former split-operon components (90). It is noteworthy that our assertion that the taxonomic placement of Marinobacter and Saccharophagus is erroneous received strong confirmation from the results of Wu and Eison (88), in whose genome tree the orders Alteromonadales, Oceanospiralles, and Pseudomonadales were interspersed and paraphyletic.…”

“…This provides enhanced opportunities for much more extensive evolutionary interpretation than is possible in other lineages, and this focus on the Gammaproteobacteria (within the larger scope of the phylum Proteobacteria) is a highlight of this article. The formal taxons of Gammaproteobacteria at the hierarchical level of the order separate into two distinct groups based on the criteria of many character states of aromatic amino acid biosynthesis, as exemplified by several recent publications that employed the cohesion group approach (6,89). Kleeb et al (45) found two comparable subdivisions in the phylogenetic tree of the cyclohexadienyl dehydratase family, which they called Gammaproteobacteria I and Gammaproteobacteria II, and the same separation is evident in the bacterial-genome tree of Wu and Eisen (88).…”

“…We found exactly the same division to be apparent in the current cohesion group analysis of Ask. These two informal "superorders" have been called the lower Gammaproteobacteria and the upper Gammaproteobacteria (6,84,89), and these designations are applied in the present analysis. Figure 3 shows a 16S rRNA tree of organisms selected from various orders of Gammaproteobacteria.…”

“…However, if on occasion they contain paralogs or xenologs having different functional roles and/or regulation, that is likely to facilitate even more valuable inferences. For example, S. coelicolor possess two paralogs in TyrCG-17 (6). One is an arogenate dehydrogenase; the other is PapC, an enzyme having a single substitution at position 154 that alters its substrate specificity and that is encoded by a gene regulated within the calcium-dependent antibiotic cluster.…”

The AlternativeTranslational Profile That Underlies the Immune-Evasive State of Persistence in Chlamydiaceae Exploits Differential Tryptophan Contents of the Protein Repertoire

“…Since the extreme variability of the N terminus seems likely to be a source of phylogenetic noise, we assembled a set of sequences that all begin with the Pmp_M domain in order to construct a tree based upon the much more conserved middle and C-terminal domains. We used the cohesion group approach (16,74,140,141) for the evolutionary analysis. This approach utilizes a process which eliminates bias caused when the sequences available do not exhibit an ideal phylogenetic spacing, i.e., some groups that have very similar sequences will contribute to overrepresentation of some amino acid residues.…”